Protein synthesis levels are increased in a subset of individuals with fragile X syndrome.

Fragile X syndrome (FXS) is a monogenic form of intellectual disability and autism spectrum disorder caused by the absence of the fragile X mental retardation protein (FMRP). In biological models for the disease, this leads to upregulated mRNA translation and as a consequence, deficits in synaptic architecture and plasticity. Preclinical studies revealed that pharmacological interventions restore those deficits, which are thought to mediate the FXS cognitive and behavioral symptoms. Here, we characterized the de novo rate of protein synthesis in patients with FXS and their relationship with clinical severity. We measured the rate of protein synthesis in fibroblasts derived from 32 individuals with FXS and from 17 controls as well as in fibroblasts and primary neurons of 27 Fmr1 KO mice and 20 controls. Here, we show that levels of protein synthesis are increased in fibroblasts of individuals with FXS and Fmr1 KO mice. However, this cellular phenotype displays a broad distribution and a proportion of fragile X individuals and Fmr1 KO mice do not show increased levels of protein synthesis, having measures in the normal range. Because the same Fmr1 KO animal measures in fibroblasts predict those in neurons we suggest the validity of this peripheral biomarker. Our study offers a potential explanation for the comprehensive drug development program undertaken thus far yielding negative results and suggests that a significant proportion, but not all individuals with FXS, may benefit from the reduction of excessive levels of protein synthesis.

Warburg effect linked to cognitive-executive deficits in FMR1 premutation.

A 55-200 CGG repeat expansion in the 5'-UTR of the fragile X mental retardation 1 (FMR1) gene is known as a premutation. Some carriers are affected by the neurodegenerative disorder fragile X-associated tremor/ataxia syndrome (FXTAS), primary ovarian insufficiency, and neurobehavioral impairments. Based on the mitochondrial dysfunction observed in fibroblasts and brain samples from carriers, as well as in neurons and brains from a mouse model of the premutation, we evaluated the presence of the Warburg effect in peripheral blood mononuclear cells (PBMCs) from 30 premutation carriers with either a rebalance of the metabolism [increasing glycolysis while decreasing oxidative phosphorylation (oxphos)] or a metabolic amplification (increasing glycolysis while maintaining/increasing oxphos). Deficits in oxphos-more pronounced in FXTAS-affected subjects-were accompanied by a shift toward glycolysis, suggesting increased glycolysis despite aerobic conditions. Differential proteomics extended these findings, unveiling a decreased antioxidant response, translation, and disrupted extracellular matrix and cytoskeleton organization with activation of prosenescence pathways. Lower bioenergetics segregated with increased incidence of low executive function, tremors, below-average IQ, and FXTAS. The combination of functional and proteomic data unveiled new mechanisms related to energy production in the premutation, showing the potential of being applicable to other psychiatric disorders to identify endophenotype-specific responses relevant to neurobiology.-Napoli, E., Song, G., Schneider, A., Hagerman, R., Eldeeb, M. A. A. A., Azarang, A., Tassone, F., Giulivi, C. Warburg effect linked to cognitive-executive deficits in FMR1 premutation.

Aging in Fragile X Premutation Carriers.

It is now recognized that FMR1 premutation carriers (PC) are at risk to develop a range of neurological, psychiatric, and immune-mediated disorders during adulthood. There are conflicting findings regarding the incidence of hypertension, hypothyroidism, diabetes, and cancer in these patients that warrant further study. A retrospective controlled study was performed in a convenience sample of 248 controls (130 men, 118 women) and 397 FMR1 PC with and without fragile X-associated tremor ataxia syndrome (FXTAS) (176 men, 221 women); all participants were at least 45 years old (men: mean 62.4, SD 9.5; women: mean 62.8, SD 9.9; p = 0.63). Memory and cognitive assessments (Wechsler Adult Intelligence Scale (WAIS-III), Wechsler Memory Scale (WMS-III)) and molecular testing (CGG repeats and FMR1-mRNA levels) were performed. Additional data included body mass index (BMI), cholesterol levels, blood pressure, hemoglobin A1c (HbA1c) levels, and medical history. A higher percentage of PC subjects self-reported having a diagnosis of hypertension (50.0 vs. 35.0 %, p = 0.006) and thyroid problems (20.4 vs. 10.0 %, p = 0.012) than control subjects. When comparing controls versus PC with FXTAS, the association was higher for diabetes (p = 0.043); however, the effect was not significant after adjusting for demographic predictors. Blood pressure, blood glucose levels, HbA1c, and BMI values were not significantly different between the two groups. The PC with FXTAS group performed consistently lower in neuropsychological testing compared with the PC without FXTAS group, but the differences were very small for all but the WAIS full-scale IQ. Based on these findings, it appears that the risk for hypertension, thyroid problems, and diabetes may be more frequent in PC with FXTAS, which will require verification in future studies.

Effect of the Low Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAP) Diet on Control of Pediatric Irritable Bowel Syndrome and Quality of Life Among a Sample of Egyptian Children: A Randomized Controlled Clinical Trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a pediatric pain-dominant functional gastrointestinal disorder that has a negative impact on all children's dimensions of quality of life. A dietary approach that focuses on limiting food elements with high fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) can be used to decrease symptoms of IBS. This study aims to evaluate the effect of low FODMAP dietary intervention on health-related quality of life among a sample of Egyptian children. METHODS: Eighty-four children aged 5-15 years old were randomly assigned to two groups, 42 patients in the low FODMAP diet group and 42 patients in the standard diet group. They received the diet for six weeks and were followed up weekly using a visual analog scale (VAS) for pain severity assessment, the Pediatric Quality of Life (PedsQL) Inventory Gastrointestinal (GI) Symptoms Module Scale, and the PedsQL Inventory Generic Core Scale to assess the physical and psychosocial functioning of the patients. RESULTS: The VAS score decreased more in the low FODMAP group, which caused a significant difference between the two groups (p<0.001). The PedsQL Inventory GI Symptoms Module score increased more among the low FODMAP group, and this caused a significant difference between the two groups (p<0.001). PedsQL Inventory Generic Core score increased more among the low FODMAPs group, and this caused a significant difference between the two groups (p<0.001). CONCLUSION: Low FODMAP dietary intervention in pediatrics for six weeks decreased abdominal pain severity, improved gastrointestinal symptoms, and improved the health-related quality of life of the affected children.

The effect of long-pulsed 1064 nm Nd:YAG laser-assisted hair removal on some skin flora and pathogens: an in vivo study.

Background The effect of NDYag on normal skin flora and pathogenic microbes has not been studied. Objectives Evaluation of immediate (before versus after each session) and delayed (pre-first session versus pre-fourth session) antimicrobial effect of Nd:YAG laser-assisted hair removal. Methods Thirty females scheduled for axillary Nd:YAG laser hair removal were included. Skin swabs were collected from the vault of the dominant axilla before and after each of the four sessions. Bacteriological cultures were performed to record the counts of total aerobes, total anaerobes, lipophilic bacteria, total staphylococci, Staphylococcus epidermidis (S. epidermidis), S. saprophyticus, S. hominis, and S. aureus. Reported changes in sweat odour and folliculitis (if present) were recorded. Results S.hominis was the predominant species in all subjects before and after all sessions. Counts of total aerobes, total anaerobes, lipophilic bacteria, total staphylococci, and S.hominis significantly decreased after all 4 sessions. A significant reduction was noted in the median colony counts before the fourth session as compared to the baseline count before the first session in total aerobes (278.9 versus 126.3 × 105 CFU/cm2, p = 0.003), total anaerobes (338.7 versus 103.7 × 105 CFU/cm2, p = 0.002) and total staphylococci (248.5 versus 105.0 × 105 CFU/cm2, p = 0.004). Most subjects reported worsened or unchanged axillary sweat odour. There was a statistically significant positive correlation between sweat odour and the counts of total aerobes (r = 0.433, p = 0.017), total anaerobes (r = 0.377, p = 0.040), total staphylococci (r = 0.383, p = 0.036) and S.hominis (r = 0.497, p = 0.005) ; lower counts were associated with a worsened odour. Limitations Small sample size; few laser sessions; short follow-up; subjective assessment of sweat odor and quantity. Conclusions Laser caused an immediate and delayed reduction in axillary aerobes, anaerobes, lipophilic bacteria, and staphylococci. This form of dysbiosis might lead to sweat odour changes.

Evaluation of efficacy of follicular unit extraction versus follicular unit extraction with platelet rich plasma in treatment of cicatricial alopecia.

BACKGROUND: Follicular unit extraction (FUE) is a minimally invasive surgery that is becoming popular in hair restoration in cicatricial alopecia (CA). AIM: Evaluation of FUE with or without platelet rich plasma (PRP) in scarring alopecia. PATIENTS AND METHODS: Twenty patients with CA were randomized into two groups. Group A (10 patients) underwent FUE, group B (10 patients) underwent FUE + PRP. PRP was injected 1 week before surgery, then monthly after surgery for 3 months. Follow up was done after 3, 6 and 12 months by calculating the density of surviving follicular units and the survival rate. RESULTS: In group A, there was statistically significant increase in mean survival rate which was 30.30%. At 3 months, 67.26% at 6 months and 78.15% at 12 months. In group B, there was a significant increase in mean survival rate being 30.14% at 3 months, 58.75% at 6 months and 69.74% at 12 months. There was no significant difference between both groups at anytime during follow up period. CONCLUSION: Follicular unit extraction is a preferred procedure for hair restoration in CA with few side effects. The role of PRP in HT is controversial. In the present study, PRP does not significantly affect the survival rate of hair grafts.

Common Indications for Referral to the Healthcare system for COVID-19 recovered patients versus Qatar Biobank study population: A descriptive analysis.

BACKGROUND AND AIM OF THE WORK: Qatar Biobank (QBB) is actively acquiring data on the range of short- and long-term health impacts associated with COVID-19. This is performed through the COVID-19 biorepository National project. In this report, we describe the most common indications for the referral to Qatar's healthcare system of COVID-19 biorepository participants in comparison with the Qatar Biobank (QBB) general population study. Methods Patients with a laboratory diagnosis of COVID-19, who were Qatar residents that could communicate in Arabic, English, Hindi and Urdu were eligible to participate in the COVID-19 biorepository project. Biological samples of Consented participants were collected on a weekly basis until recovery, and then monthly for a year. Participants were also offered a bone density scan three months after recovery and non-contrast MRI brain and whole-body scan six months after recovery. Number of participants requiring referral for medical follow up after recovery for any abnormal clinically significant findings were recorded and statistically compared to general population referred participants Results: The majority of referrals for the general population study was for osteopenia versus diabetes for the COVID-19 biorepository project Conclusion Descriptive analysis of the referral data of the COVID-19 participants and QBB general population (not previously affected by the virus) shows a clear difference between the two populations' reasons for referrals. Diabetes for COVID 19 recovered participants versus osteopenia for general population Keywords: COVID19, Reason for Referrals, Diabetes, Qatar biobank.

Cicatricial alopecia: do clinical, trichoscopic, and histopathological diagnosis agree?

INTRODUCTION: Cicatricial alopecia (CA) results from irreversible destruction and fibrosis of hair follicles. Trichoscopy offers a noninvasive method for diagnosis. METHODS: Thirty-two patients clinically diagnosed with CA were subjected to trichoscopy and histopathology assessment. The sensitivity and specificity of clinical and trichoscopic diagnoses were compared to histopathology. RESULTS: Thirty-two patients were clinically diagnosed as follows: 12 with discoid lupus erythematosus, four with lichen planopilaris (LPP), two with frontal fibrosing alopecia (FFA), three with folliculitis decalvans (FD), nine with central cicatricial centrifugal alopecia (CCCA), and two with long-term alopecia areata. Trichocopy revealed discoid lupus in 13 patients, LPP in nine, FFA in two, FD in three, central centrifugal alopecia in four, and pseudopelade in one. Histopathology confirmed discoid lupus in 13 patients, LPP in five, FFA in two, FD in three, CCCA in six, pseudopelade in two, and sarcoidosis in one. The sensitivity and specificity of clinical diagnosis were 69.2% and 84.2% in discoid lupus, 40.0% and 92.6% in LPP, 100.0% and 100.0% in FFA, 66.7% and 96.6% in FD, and 66.7% and 80.8% in central centrifugal alopecia. The sensitivity and specificity of trichoscopy were 84.6% and 89.5% in discoid lupus, 100.0% and 85.2% in LPP, 100.0% and 100.0% in FFA and FD, 66.7% and 100.0% in central centrifugal alopecia, and 50.0% and 100.0% in pseudopelade. CONCLUSIONS: Trichoscopy can be equivalent to histopathology for diagnosing some cases of CA.

Photodynamic therapy using methylene blue and intense pulsed light versus intense pulsed light alone in treatment of verruca: A randomized controlled study.

BACKGROUND: Many therapeutic modalities are available for treatment of warts, but no single therapy is universally effective. Photodynamic therapy (PDT) using intralesional methylene blue (MB) followed by intense pulsed light (IPL) could be a successful option for treatment by several mechanisms. METHODS: This prospective randomized controlled trial was carried out on eighty patients with verrucae. Patients were randomized into three groups; group A (30 patients) received MB/IPL/PDT sessions, group B (30 Patients) received IPL sessions, and group C (control). Response was assessed by clinical and dermoscopy score (0,1, 2, or 3 according to extent of clinical and dermoscopic resolution), cure rate (percent of verrucae clinically and dermoscopy cleared), and imageJ analysis (surface area of wart and haemorrhagic structures or vessels). RESULTS: Clinical and dermoscopic clearance was achieved in 43.3% and 20% of patients in groups A and B respectively. Cure rate was 40.9% for group A compared to 23.4% for group B. ImageJ analysis revealed more reduction of surface area in group A being 80.05 ± 27.12% for verrucae and 89.28 ± 19.19% for vessels and haemorrhagic dots compared to 48.16 ± 34.21% and 65.99 ± 30.58% in group B. CONCLUSIONS: MB/IPL/PDT is an effective option for treatment of warts with a success rate of around 40%, based on clinical and dermoscopic assessment. The efficacy was found to be higher on using imageJ utilizing both the surface area of the wart and surface area of vessels and haemorrhagic dots with the latter being more effected by treatment.

A Randomized, Double-Blind, Placebo-Controlled Trial of Low-Dose Sertraline in Young Children With Fragile X Syndrome.

OBJECTIVE: Observational studies and anecdotal reports suggest that sertraline, a selective serotonin reuptake inhibitor, may improve language development in young children with fragile X syndrome (FXS). METHODS: The authors evaluated the efficacy of 6 months of treatment with low-dose sertraline in a randomized, double-blind, placebo-controlled trial in 52 children with FXS aged 2 to 6 years. RESULTS: Eighty-one subjects were screened for eligibility, and 57 were randomized to sertraline (27) or placebo (30). Two subjects from the sertraline arm and 3 from the placebo arm discontinued. Intent-to-treat analysis showed no difference from placebo on the primary outcomes: the Mullen Scales of Early Learning (MSEL) expressive language (EL) age equivalent and Clinical Global Impression Scale-Improvement. However, analyses of secondary measures showed significant improvements, particularly in motor and visual perceptual abilities and social participation. Sertraline was well tolerated, with no difference in side effects between sertraline and placebo groups. No serious adverse events occurred. CONCLUSION: This randomized controlled trial of 6 months of sertraline treatment showed no primary benefit with respect to early EL development and global clinical improvement. However, in secondary exploratory analyses, there were significant improvements seen on motor and visual perceptual subtests, the cognitive T score sum on the MSEL, and on one measure of social participation on the Sensory Processing Measure-Preschool. Furthermore, post hoc analysis found significant improvement in early EL development as measured by the MSEL among children with autism spectrum disorder on sertraline. Treatment appears safe for this 6-month period in young children with FXS, but the authors do not know the long-term side effects of this treatment. These results warrant further studies of sertraline in young children with FXS using refined outcome measures as well as longer term follow-up studies to address long-term side effects of low-dose sertraline in early childhood.